The U.S. Supreme Court will have on its docket one of two cases being watched closely by molecular diagnostics companies looking for answers about what intellectual property they can patent and what they can’t.

During the new term, which begins on October 3, Mayo Collaborative Services (doing business as Mayo Medical Laboratories) and Mayo Clinic Rochester will appeal to the justices to overturn the decision by the Court of Appeals for the Federal Circuit last December that upheld two diagnostic method patents owned by Prometheus Laboratories. At issue are patents that cover the methods of dosage calibration for thiopurine drugs for gastrointestinal and nongastrointestinal autoimmune diseases. The methods were designed to take into account the context of a treatment regime based on the individual patient’s metabolism.

The decision the Supreme Court reaches in Prometheus Laboratories, Inc. v. Mayo Collaborative Services et al. is expected to influence the high court’s thinking in a second molecular diagnostics case likely to come before it in the next year or so.

Myriad Genetics is seeking to protect seven patents related to breast cancer susceptibility genes 1 and 2 (BRCA1 and BRCA2) and its method for analyzing sequences of those genes for mutations associated with breast cancer against a legal challenge by several medical associations and individual doctors, assisted by the American Civil Liberties Union and Public Patent Foundation.

The Prometheus case, Jonathan D.J. Loeb, Ph.D., a partner in the law firm Dechert, told GEN, “may dictate the outcome in Myriad and may end up being the case that ends up defining the law for this area of genotyping, diagnostics, and personalized medicine. Until the Supreme Court rules in Prometheus, which should be early next year, or there’s some final resolution in Myriad, it’s sort of premature to be able to map the landscape of the DNA diagnostics business into the future,” Dr. Loeb added.

In the Courts

In July a three-judge panel of the Federal Circuit decided Association for Molecular Pathology v. US Patent and Trademark Office by finding Myriad’s gene claims patentable as well as its methods of screening for cancer compounds. Regarding the latter, the court reasoned that the steps involved in growing cells containing a BRCA1 or BRCA2 gene and in manipulating the growth of those cells in the presence or absence of a cancer therapeutic did not just constitute observation but involved transformation of the cell culture.

However, the Federal Circuit also found that Myriad’s claims for the mutation analysis were not patentable, dismissing them as “abstract mental processes” and contrasting them with Prometheus’ claims by arguing that: “Myriad’s claims, in contrast, do not include the step of ‘determining’ the sequence of BRCA genes by, e.g., isolating the genes from a blood sample and sequencing them or any other necessarily transformative step.” Late last month, both ACLU and Myriad filed separate petitions seeking a re-review of the case.

The Prometheus case started in June 2004 when Prometheus sued Mayo in U.S. District Court, alleging that an announced (but never marketed) Mayo Medical Laboratories diagnostic test infringed two Prometheus patents. Mayo’s test measured the same metabolites as Prometheus’ test, but Mayo’s test used different levels to determine toxicity of the two metabolites.

Mayo has countered that Prometheus’ patents are invalid and unenforceable because the claims were based on subject matter that is unpatentable as they impermissibly claimed natural phenomena—the correlations between, on the one hand, thiopurine drug metabolite levels and, on the other hand, efficacy and toxicity—and that the claims wholly preempt use of the natural phenomena.

After some back and forth through the judicial system, the Federal Circuit sided with Prometheus in December 2010. The court stated that the firm’s claims passed a revised In re Bilski machine-or-transformation standard. Prometheus’ claims, the circuit court ruled, recited specific treatment steps, not just correlations themselves, and involved a specific application of natural correlationism, namely the treatment of a specific disease by administering specific drugs and measuring specific metabolites.

Writing Patents

Lisa A. Haile, Ph.D., a partner at DLA Piper U.S. and co-chair of the firm’s global life sciences sector group, told GEN she does not think a decision upholding Prometheus’ patents is likely to affect product development.

“From the perspective of product development per se, I don’t think it changes anything. I think it’s really just an issue of how you protect what you’re doing, what your tests are, that sort of thing,” Dr. Haile noted.

Where a decision to uphold Prometheus will likely prove most significant is in the writing of patent claims. “I would typically not write the claim saying that you isolate the DNA and then sequence it, and then do the analysis, because anybody could avoid infringing it. But I want to draft a claim that’s going to be valid, so I might have to put in that isolating and sequencing step or steps. At the same time, am I really providing a claim that has value because it’s so easy to avoid infringing it?

“We’re going to have to think hard about strategically how to draft these claims to fit within the court’s requirements while still keeping in mind that you have to capture infringers,” Dr. Haile added. If the Supreme Court upholds the Prometheus v. Mayo decision, she advised, “then I think people may need to go back and look at their existing patents and existing pending applications and seriously consider making amendments to the claims, adding in these additional transformative steps.”

Dr. Loeb agreed, also advising that diagnostics innovators produce methods that involve transformative steps. “The Myriad case provides a bit of a roadmap of what the innovators should be doing when they’re trying to claim these inventions.” He cited the Federal Circuit’s Myriad decision, which contrasted Myriad with Prometheus by noting that Myriad’s claims do not include such transformative steps.

That’s easier said than done, he added, given the development of numerous ways to detect and compare the gene sequences of individuals. “The question becomes, ‘what kinds of steps can you describe that are transformative yet general enough to cover all the different ways that you can test genotypes today and, more importantly, tomorrow?

“Essentially, the heart of these inventions is the particular correlation between a genotype and a disease or the effectiveness of a drug. Once you recognize that correlation, how do you turn that into a patentable invention that includes a method with transformative steps that will cover all the different ways that competitors could later attempt to use the correlation that you discovered but entirely different molecular technologies for assessing genotypes?”

In the worst case, according to Dr. Loeb, the court cases will make it more difficult for diagnostic firms to get strong protections for their inventions than is the case under current law. For as long as the situation is unsettled, though, “diagnostic companies and diagnostic innovators certainly have opportunities to get meaningful patent protection in this area,” Dr. Loeb added.

Balancing Public Concern and Business Interests

An issue raised by the Myriad case is reflected in the America Invents Act, the new patent reform measure passed by the Senate on September 8. One provision of America Invents requires the USPTO to study how to ensure the availability of confirming genetic diagnostic tests where gene patents and exclusive licensing for primary genetic diagnostic tests exist.

Dr. Loeb said the provision is designed to address a public policy concern stemming from gene patentability: that allowing Myriad and other holders of patents to genetic tests to exclusively license them may prevent doctors and patients from getting independent second opinion diagnostic testing.

“Congress would have to further act to overrule Myriad. It’s hard to see what action USPTO Director David Kappos would recommend. Prohibiting exclusive licensing of a specific type of patented invention would be nearly unprecedented in patent law,” Dr. Loeb pointed out.

All the more reason why that scenario is less likely than one in which the Supreme Court abides by its own precedent in several recent decisions of tilting toward business interests and upholding the patent claims of Prometheus and Myriad. As Dr. Loeb correctly noted, the decisions in those cases will constitute a roadmap to patenting and ultimately commercializing molecular diagnostics tests and the genetic material to be used in them.

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